Variant chrX-153982096-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_003492.3(TMEM187):c.34G>C(p.Val12Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000982 in 1,211,720 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 32 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000070 ( 0 hom., 1 hem., cov: 25)

Exomes 𝑓: 0.00010 ( 0 hom. 31 hem. )

Consequence

TMEM187
NM_003492.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.77

Variant links:

Genes affected

TMEM187 (HGNC:13705): (transmembrane protein 187) This gene consists of two exons and encodes a multi-pass membrane protein. An alternatively spliced transcript variant encoding the same protein has been found, but its biological validity is not determined. [provided by RefSeq, May 2010]

TMEM187 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36271217).

BS2

High Hemizygotes in GnomAdExome4 at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM187	NM_003492.3 linkuse as main transcript	c.34G>C	p.Val12Leu	missense_variant	2/2	ENST00000369982.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TMEM187	ENST00000369982.5 linkuse as main transcript	c.34G>C	p.Val12Leu	missense_variant	2/2	1	NM_003492.3	P1
TMEM187	ENST00000425274.1 linkuse as main transcript	c.34G>C	p.Val12Leu	missense_variant	2/2	5
TMEM187	ENST00000431598.1 linkuse as main transcript	c.34G>C	p.Val12Leu	missense_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000704

AC:

AN:

113662

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

35792

show subpopulations

Gnomad AFR

AF:

0.0000319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000131

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000220

AC:

AN:

181851

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

66819

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000496

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

111

AN:

1098058

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

363496

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.000304

GnomAD4 genome

AF:

0.0000704

AC:

AN:

113662

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

35792

show subpopulations

Gnomad4 AFR

AF:

0.0000319

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000131

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.34G>C (p.V12L) alteration is located in exon 2 (coding exon 1) of the TMEM187 gene. This alteration results from a G to C substitution at nucleotide position 34, causing the valine (V) at amino acid position 12 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.069

T;.;.

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.52

T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.4

M;.;.

MutationTaster

Benign

0.53

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.4

N;N;D

REVEL

Benign

0.25

Sift

Pathogenic

0.0

D;D;.

Sift4G

Benign

0.089

T;D;D

Polyphen

1.0

D;.;.

Vest4

0.50

MutPred

0.23

Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);

MVP

0.27

MPC

0.37

ClinPred

0.65

GERP RS

4.2

Varity_R

0.51

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over